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• W1539779969 abstract "SummaryBackground: Alanine aminotransferase (ALT) predicts the development of Type 2 diabetes mellitus and cardiovascular disease in Caucasian subjects. Objectives: This study aimed to determine the incidence of an elevated ALT and its relationship to metabolic and atherothrombotic risk factors in a healthy British South Asian population. Patients/methods: One hundred and forty‐three participants from the West Yorkshire community were recruited randomly from general practice registers and were grouped according to whether their ALT was above or within the normal range (cut‐off 35 IU L−1) and examined for differences in metabolic and atherothrombotic risk factors. All participants were originally from South Asia, with their grandparents being born in India, Pakistan, or Bangladesh. Results: The incidence of a raised ALT was 24%. Those with a raised ALT had a more adverse metabolic profile, with significantly higher body mass index, waist/hip ratio, fasting insulin, glucose, homeostasis model assessment homeostasis model assessment insulin resistance (HOMA‐IR), and triglycerides, and lower high‐density lipoprotein (HDL) cholesterol. Fifty per cent had the metabolic syndrome [International Diabetes Federation (IDF) criteria]. They also had a more adverse atherothrombotic profile, with higher tissue‐type plasminogen activator and plasminogen activator inhibitor‐1 (PAI‐1) antigen. In accordance, the group as a whole showed a positive correlation of ALT (age‐adjusted) with waist/hip ratio, insulin, glucose, triglycerides, PAI‐1 antigen, factor XIII B subunit, and FXII, and a negative correlation with HDL cholesterol. Conclusion: Raised ALT is common in apparently healthy British South Asians, and is significantly associated with an adverse metabolic and atherothrombotic risk profile. Background: Alanine aminotransferase (ALT) predicts the development of Type 2 diabetes mellitus and cardiovascular disease in Caucasian subjects. Objectives: This study aimed to determine the incidence of an elevated ALT and its relationship to metabolic and atherothrombotic risk factors in a healthy British South Asian population. Patients/methods: One hundred and forty‐three participants from the West Yorkshire community were recruited randomly from general practice registers and were grouped according to whether their ALT was above or within the normal range (cut‐off 35 IU L−1) and examined for differences in metabolic and atherothrombotic risk factors. All participants were originally from South Asia, with their grandparents being born in India, Pakistan, or Bangladesh. Results: The incidence of a raised ALT was 24%. Those with a raised ALT had a more adverse metabolic profile, with significantly higher body mass index, waist/hip ratio, fasting insulin, glucose, homeostasis model assessment homeostasis model assessment insulin resistance (HOMA‐IR), and triglycerides, and lower high‐density lipoprotein (HDL) cholesterol. Fifty per cent had the metabolic syndrome [International Diabetes Federation (IDF) criteria]. They also had a more adverse atherothrombotic profile, with higher tissue‐type plasminogen activator and plasminogen activator inhibitor‐1 (PAI‐1) antigen. In accordance, the group as a whole showed a positive correlation of ALT (age‐adjusted) with waist/hip ratio, insulin, glucose, triglycerides, PAI‐1 antigen, factor XIII B subunit, and FXII, and a negative correlation with HDL cholesterol. Conclusion: Raised ALT is common in apparently healthy British South Asians, and is significantly associated with an adverse metabolic and atherothrombotic risk profile. Accumulating evidence from large prospective epidemiological studies suggests that alanine aminotransferase (ALT) is an independent predictor for the development of Type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) [1Ekstedt M. Franzen L.E. Mathiesen U.L. Thorelius L. Holmqvist M. Bodemar G. Kechagias S. Long‐term follow‐up of patients with NAFLD and elevated liver enzymes.Hepatology. 2006; 44: 865-73Crossref PubMed Scopus (1808) Google Scholar, 2Sattar N. Scherbakova O. Ford I. O’Reilly D.S. Stanley A. Forrest E. Macfarlane P.W. Packard C.J. Cobbe S.M. Shepherd J. Elevated alanine aminotransferase predicts new‐onset type 2 diabetes independently of classical risk factors, metabolic syndrome, and C‐reactive protein in the west of Scotland coronary prevention study.Diabetes. 2004; 53: 2855-60Crossref PubMed Scopus (290) Google Scholar, 3Hanley A.J. Williams K. Festa A. Wagenknecht L.E. D’Agostino Jr, R.B. Kempf J. Zinman B. Haffner S.M. Elevations in markers of liver injury and risk of type 2 diabetes: the insulin resistance atherosclerosis study.Diabetes. 2004; 53: 2623-32Crossref PubMed Scopus (304) Google Scholar, 4Wannamethee S.G. Shaper A.G. Lennon L. Whincup P.H. Hepatic enzymes, the metabolic syndrome, and the risk of type 2 diabetes in older men.Diabetes Care. 2005; 28: 2913-18Crossref PubMed Scopus (217) Google Scholar, 5Hanley A.J. Williams K. Festa A. Wagenknecht L.E. D’Agostino Jr, R.B. Haffner S.M. Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study.Diabetes. 2005; 54: 3140-7Crossref PubMed Scopus (346) Google Scholar] in Caucasian subjects. T2DM and CVD are underpinned by the presence of insulin resistance and a cluster of metabolic, inflammatory and prothrombotic abnormalities known as the metabolic syndrome. Obesity, and especially the accumulation of visceral fat, is central to the development of insulin resistance and the metabolic syndrome, due to the active secretory role of adipose tissue. An increased ALT level, in the absence of known liver disease, most commonly reflects liver fat deposition, and is representative of the presence of visceral fat, which is central to the development of insulin resistance and the atherothrombotic risk factor cluster seen in T2DM and CVD [6Marchesini G. Brizi M. Bianchi G. Tomassetti S. Bugianesi E. Lenzi M. McCullough A.J. Natale S. Forlani G. Melchionda N. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome.Diabetes. 2001; 50: 1844-50Crossref PubMed Scopus (1978) Google Scholar]. South Asians have a higher incidence of the metabolic syndrome and T2DM than their Caucasian counterparts, with an associated increased rate of mortality from coronary artery disease and stroke [7Wild S. McKeigue P.M. Cross sectional analysis of mortality by country of birth in England and Wales, 1970–92.BMJ. 1997; 314: 705-10Crossref PubMed Scopus (355) Google Scholar]. Classic risk factors are not able to explain this increased risk [8McKeigue P.M. Shah B. Marmot M.G. Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians.Lancet. 1991; 337: 382-6Abstract PubMed Scopus (1380) Google Scholar]. The aim of the present study was to determine the incidence of a raised ALT level and its relationship to metabolic and atherothrombotic risk factors in a clinically healthy British South Asian population. One‐hundred and forty‐three apparently clinically healthy South Asian subjects with mean age of 43 years (43% females) were recruited randomly from general practitioners’ lists from West Yorkshire as previously described [9Kain K. Catto A.J. Young J. Bamford J. Bavington J. Grant P.J. Insulin resistance and elevated levels of tissue plasminogen activator in first‐degree relatives of South Asian patients with ischemic cerebrovascular disease.Stroke. 2001; 32: 1069-73Crossref PubMed Scopus (22) Google Scholar]. The subjects were contacted by mail. A volunteer information sheet written in both English and various South Asian languages (namely Gujrati, Punjabi, Bengali, Hindi and Urdu) according to subject’s ethnic background was sent. More than 50% of the subjects contacted agreed to take part in the study. Subjects were seen in their homes or invited to a hospital research clinic. Self‐reported history and information on medication use was recorded for all persons. All the subjects were free of clinically detectable stroke, ischemic heart disease, and peripheral vascular disease. All subjects were of British South Asian origin (India, Pakistan, or Bangladesh), and their four grandparents were from one of these countries. Subjects with mixed parentage were not recruited. The local research ethics committees provided ethical approval. All subjects provided informed written consent to the investigations, which were carried out in accordance with the Declaration of Helsinki. Height and weight were recorded without shoes and in light clothing. Body mass index (BMI) was calculated from weight in kilograms divided by height squared in meters. Waist/hip ratio (WHR) was calculated by taking the measurement at minimum abdominal girth and dividing it by measurement at maximal protrusion of the hips at the level of the symphysis pubis, to the nearest 0.5 cm. Blood pressure was taken to the nearest 2 mmHg after 15 min of rest and as the mean of three readings, with subjects lying. Smoking history was classified into subjects who never smoked and smokers (ex‐smokers or current smokers). A history of alcohol intake was reliant on self‐reporting. After an overnight fast of at least 10 h and rest for 20 min, fasting blood samples (without venous stasis) were drawn from an antecubital vein with a 19‐gauge needle. Blood was taken into 0.9% iced citrate (pH 8.8) at a ratio of nine parts blood to one part citrate for assay of tissue‐type plasminogen activator (t‐PA), plasminogen activator inhibitor‐1 (PAI‐1) antigen, and PAI‐1 activity, and into iced lithium heparin for the determination of insulin levels. Samples were centrifuged at 2560 × g and 4 °C for 30 min. Aliquots of plasma were snap‐frozen in liquid nitrogen and stored at − 40 °C until assay. Assessment of ALT was made by routine liver function tests in the biochemistry department. At the time of the study, the normal reference ranges for the local population were ALT 0–35 IU L−1, gamma‐glutamyl transferase (GGT) 8–48 U dL−1, alkaline phosphatase (ALP) 70–300 IU L−1, total protein 67–82 g L−1 and total bilirubin 3–15 mg dL−1. Measurement of plasma glucose (by the glucose oxidase method), cholesterol and triglycerides were done with a Hitachi 747 autoanalyzer (Boehringer Mannheim, Mannheim, Germany). High density lipoprotein (HDL) cholesterol was measured with a Hitachi 717 autoanalyzer (Boehringer Mannheim) after removal of chylomicrons. Glycosylated hemoglobin (HbA1c) was measured using a Glycomat autoanalyzer (Ciba Corning, Halstead, UK), with a reference range of 4.5–6.5%. PAI‐1 antigen, t‐PA and plasma insulin were measured by the enzyme‐linked immunosorbent assay method. The interassay and intra‐assay coefficients of variation were 9.5% and 7% for t‐PA, 9.7% and 6.0% for PAI‐1 antigen, and 5.6% and 5.3% at 18 μIU mL−1 and 9.8% and 3.0% at 84 μIU mL−1 for insulin, respectively. Values for insulin resistance were calculated from the homeostasis model assessment (HOMA) [10Matthews D. Hosker J.P. Rudenski A.S. Naylor B.A. Treacher D.F. Turner R.C. Homeostasis model assessment: insulin resistance and beta‐cell function from fasting plasma glucose and insulin concentrations in man.Diabetologia. 1985; 28: 412-19Crossref PubMed Scopus (25651) Google Scholar], which assumes that normal‐weight, healthy subjects aged < 35 years have 100%β‐cell function and an insulin resistance of unity. HOMA was expressed as a product of insulin and glucose levels divided by 22.5. The metabolic syndrome was defined on the basis of International Diabetes Federation (IDF) criteria [11Alberti K.G. Zimmet P. Shaw J. The metabolic syndrome – a new worldwide definition.Lancet. 2005; 366: 1059-62Abstract Full Text Full Text PDF PubMed Scopus (5941) Google Scholar] as ethnic specific visceral obesity with waist circumference in men > 90 cm and in women > 80 cm, plus any two out of three of the following: raised triglycerides > 1.7 mmol L−1 (150 mg dL−1) or specific treatment for this lipid abnormality, reduced HDL cholesterol < 1.03 mmol L−1 (40 mg dL−1) in men and < 1.29 mmol L−1 (50 mg dL−1) in women or specific treatment for this lipid abnormality, raised blood pressure, systolic 130 mmHg, and diastolic 85 mmHg, or treatment of previously diagnosed hypertension, raised fasting plasma glucose, 5.6 mmol L−1 (100 mg dL−1), or previously diagnosed T2DM. Values for ALT, BMI, WHR, fasting blood glucose, HBA1c, triglycerides, HDL cholesterol, low‐density lipoprotein (LDL) cholesterol, insulin, PAI‐1 antigen and PAI‐1 activity were log‐transformed to achieve near‐normal distribution. Subjects were divided into two groups according to ALT levels ≤ 35 and > 35 IU L−1. Differences in continuous variables between the groups were assessed by independent sample t‐test. Differences in categorical data between the two groups were assessed by χ2 test. Partial age‐adjusted correlation was used to assess the relationship of levels of ALT with other continuous variables. A univariate general linear model of analysis was used to study the differences in mean levels of insulin, PAI‐1 antigen and t‐PA antigen between the two groups after adjustment for covariates. Statistical significance was taken as P<0.05. Finally, we carried out stepwise regression analysis to detect independent risk factors for ALT. All statistical analyses were performed with SPSS for Windows version 12.0 (SPSS Inc. Chicago, IL, USA). The clinical characteristics of the subjects are shown in Table 1. Data on ALT were available for 116 of the 143 subjects. There were no differences in age, sex, HOMA (insulin resistance), metabolic syndrome and PAI‐1 antigen between subjects with or without ALT data.Table 1Clinical characteristics of British South Asian subjects, according to alanine aminotransferase (ALT) levelsALT < 35 IU L−1ALT > 35 IU L−1PNumber of subjects8828Age (years)45 (42–48)41 (37–44)0.17Gender – females (%)4311< 0.001BMI (kg m−2)24.9 (23.8–25.9)27.5 (26.0–29.2)0.01Waist (cm)89 (86–92)98 (93–102)0.002WHR0.88 (0.86–0.89)0.96 (0.93–1.0)< 0.001Current smokers (%)2140.03Alcohol intake (units week−1)7 (2–12)6 (3 to10)0.74Systolic blood pressure (mmHg)129 (124–133)131 (124–138)0.54Diastolic blood pressure (mmHg)81 (78–84)88 (82–93)0.04BMI, body mass index; WHR, waist/hip ratio; bold values, differences significant. Data presented as mean (95% confidence interval) unless detailed otherwise. Open table in a new tab BMI, body mass index; WHR, waist/hip ratio; bold values, differences significant. Data presented as mean (95% confidence interval) unless detailed otherwise. The incidence of a raised ALT (> 35 IU L−1) in the 116 subjects was 24%. Subjects with a raised ALT were significantly more likely to be male smokers and they were also more overweight, with a significantly higher BMI and WHR (27.5 vs. 24.8 kg m−2, P = 0.01, 0.96 vs. 0.88, P = < 0.001). There were no female smokers. The metabolic and atherothrombotic data of the two groups of subjects are shown in Table 2, Table 3 respectively. Subjects with a raised ALT had an adverse metabolic profile with significantly higher fasting insulin, glucose, insulin resistance (HOMA‐IR), and triglycerides, and lower HDL cholesterol. Fifty per cent of the subjects with raised ALT had the metabolic syndrome, as compared to 31% of those with a normal ALT (P = 0.007) (IDF criteria). They also had an adverse thrombotic profile, with higher levels of both t‐PA and PAI‐1 antigen. However, the difference in PAI‐1 antigen disappeared after adjustment for WHR, triglycerides or insulin. The difference in t‐PA also disappeared after adjustment for WHR,. but persisted after adjustment for triglycerides.Table 2Metabolic characteristics of British South Asian subjects, according to alanine aminotransferase (ALT) levelsALT < 35 IU L−1ALT > 35 IU L−1PFasting blood glucose (mmol L−1)5.0 (4.8–5.2)5.6 (5.1–6.1)0.02HbA1c (%)5.2 (5.0–5.3)5.7 (5.3–6.1)0.007Fasting insulin (mU L−1)7.4 (6.1–8.8)15.6 (11.4–21.3)< 0.001Insulin resistance (HOMA)1.6 (1.3–2.0)3.9 (2.8–5.4)< 0.001Total cholesterol (mmol L−1)5.0 (4.8–5.2)5.2 (4.8–5.7)0.28HDL cholesterol (mmol L−1)1.2 (1.1–1.3)0.9 (0.8–1.0)< 0.001Triglycerides (mmol L−1)1.3 (1.1–1.4)2.2 (1.7–2.7)< 0.001Metabolic syndrome (IDF) (%)31500.007Alkaline phosphatase (IU L−1)181 (167–195)185 (167–204)0.74Bilirubin (mg dL−1)10 (9–11)11 (9–13)0.28GGT (U L−1)19 (16–21)54 (42–70)< 0.001Total protein (g dL−1)77 (76–77)79 (78–80)0.006HbA1c, glycosylated hemoglobin; HOMA, homeostasis model assessment; HDL, high‐density lipoprotein; GGT, gamma‐glutamyl transferase. Data presented as mean (95% confidence interval) unless detailed otherwise. Open table in a new tab Table 3Atherothrombotic characteristics of British South Asian subjects, according to alanine aminotransferase (ALT) levelsALT < 35 IU L−1ALT > 35 IU L−1Pt‐PA (ng mL−1)8.1 (7.3–8.9)10.5 (9.4–11.6)0.003PAI‐1 antigen (U mL−1)9.0 (7.3–11.0)24.5 (19.1–31.4)< 0.0001Fibrinogen (g L−1)3.07 (2.91–3.23)2.96 (2.73–3.21)0.50Factor VII antigen (%)96.9 (92.6–101.2)98.4 (89.2–107.7)0.75VWf (IU mL−1)1.20 (1.10–1.30)1.21 (1.03–1.41)0.96t‐PA, tissue‐type plasminogen activator; PAI‐1, plasminogen activator inhibitor‐1; VWF, von Willebrand factor. Data presented as mean (95% confidence interval) unless detailed otherwise. Open table in a new tab HbA1c, glycosylated hemoglobin; HOMA, homeostasis model assessment; HDL, high‐density lipoprotein; GGT, gamma‐glutamyl transferase. Data presented as mean (95% confidence interval) unless detailed otherwise. t‐PA, tissue‐type plasminogen activator; PAI‐1, plasminogen activator inhibitor‐1; VWF, von Willebrand factor. Data presented as mean (95% confidence interval) unless detailed otherwise. As ALT levels even in the normal range have been shown to correlate with non‐alcoholic fatty liver disease (NAFLD) and cardiovascular risk factors, we looked for a relationship between ALT levels and metabolic and atherothrombotic risk factors in all subjects. In this analysis, a positive correlation of ALT (age‐adjusted) with WHR, insulin, glucose, triglycerides, PAI‐1 antigen, factor FXIII B subunit, and FXII, and a negative correlation with HDL cholesterol, were demonstrated (Table 4). In a stepwise regression model with ALT as the dependent variable and age, sex, current smoking, insulin, HDL cholesterol, WHR, triglycerides, fasting glucose, t‐PA and PAI‐1 antigen as covariates, only sex and HDL were independent predictors of ALT (R2 = 0.421, P < 0.0001).Table 4Age‐adjusted partial correlation coefficient of alanine aminotransferase (ALT)VariablesrPBody mass index0.210.07Waist/hip ratio0.49< 0.0001Systolic blood pressure0.250.04Diastolic blood pressure0.350.002Blood glucose0.360.002Insulin0.320.007Insulin resistance (HOMA)0.370.001HbA1c0.310.008HDL cholesterol− 0.61< 0.0001Triglycerides0.42< 0.0001Gamma‐glutamyl transferase0.61< 0.0001Total protein0.260.007Tissue‐type plasminogen activator antigen0.43< 0.0001Plasminogen activator‐1 antigen0.46< 0.0001Fibrinogen− 0.0840.48von Willebrand factor0.120.31aFXII0.310.008FXIII B subunit0.240.05FVII antigen− 0.060.61HOMA, homeostasis model assessment; HbA1c, glycosylated hemoglobin; HDL, high‐density lipoprotein. Open table in a new tab HOMA, homeostasis model assessment; HbA1c, glycosylated hemoglobin; HDL, high‐density lipoprotein. The results of this study have shown that clinically healthy British South Asian subjects have a high incidence of an asymptomatic, elevated ALT level. In addition, we have demonstrated that this small increase in ALT is associated with a significantly increased risk of the metabolic syndrome and associated clustering of metabolic and atherothrombotic risk factors. Studies that have reported the incidence of a raised ALT in other populations have shown a incidence ranging from 1–6% in healthy Caucasians to 7% in Caucasians with diabetes [4Wannamethee S.G. Shaper A.G. Lennon L. Whincup P.H. Hepatic enzymes, the metabolic syndrome, and the risk of type 2 diabetes in older men.Diabetes Care. 2005; 28: 2913-18Crossref PubMed Scopus (217) Google Scholar, 12Henderson J. Neithercut W.D. Spooner R.J. Frier B.M. Glycemic control and raised serum alanine aminotransferase activity in treated diabetes mellitus.Clin Biochem. 1988; 21: 245-7Crossref PubMed Scopus (3) Google Scholar, 13Clark J.M. Brancati F.L. Diehl A.M. The prevalence and etiology of elevated aminotransferase levels in the United States.Am J Gastroenterol. 2003; 98: 960-7Crossref PubMed Scopus (1092) Google Scholar]. A study in healthy Mexican Americans gave a incidence of 1–6% [14Meltzer A.A. Everhart J.E. Association between diabetes and elevated serum alanine aminotransferase activity among Mexican Americans.Am J Epidemiol. 1997; 146: 565-71Crossref PubMed Scopus (59) Google Scholar], whereas two studies have shown the incidence to be 26% in healthy Korean and Japanese populations [15Oh S.Y. Cho Y.K. Kang M.S. Yoo T.W. Park J.H. Kim H.J. Park D.I. Sohn C.I. Jeon W.K. Kim B.I. Son B.H. Shin J.H. The association between increased alanine aminotransferase activity and metabolic factors in nonalcoholic fatty liver disease.Metabolism. 2006; 55: 1604-9Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar, 16Yamada J. Tomiyama H. Yambe M. Koji Y. Motobe K. Shiina K. Yamamoto Y. Yamashina A. Elevated serum levels of alanine aminotransferase and gamma glutamyltransferase are markers of inflammation and oxidative stress independent of the metabolic syndrome.Atherosclerosis. 2006; 189: 198-205Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar]. However, comparisons between these studies are difficult, due to the unmatched nature of the populations and the use of different cut‐off levels for ALT and interlaboratory variability. A weakness of our study is that we do not have a matched local control population with which to compare these incidence figures. Our study findings lend support to studies previously performed in Caucasian subjects linking an elevated ALT to metabolic [1Ekstedt M. Franzen L.E. Mathiesen U.L. Thorelius L. Holmqvist M. Bodemar G. Kechagias S. Long‐term follow‐up of patients with NAFLD and elevated liver enzymes.Hepatology. 2006; 44: 865-73Crossref PubMed Scopus (1808) Google Scholar, 2Sattar N. Scherbakova O. Ford I. O’Reilly D.S. Stanley A. Forrest E. Macfarlane P.W. Packard C.J. Cobbe S.M. Shepherd J. Elevated alanine aminotransferase predicts new‐onset type 2 diabetes independently of classical risk factors, metabolic syndrome, and C‐reactive protein in the west of Scotland coronary prevention study.Diabetes. 2004; 53: 2855-60Crossref PubMed Scopus (290) Google Scholar, 3Hanley A.J. Williams K. Festa A. Wagenknecht L.E. D’Agostino Jr, R.B. Kempf J. Zinman B. Haffner S.M. Elevations in markers of liver injury and risk of type 2 diabetes: the insulin resistance atherosclerosis study.Diabetes. 2004; 53: 2623-32Crossref PubMed Scopus (304) Google Scholar, 4Wannamethee S.G. Shaper A.G. Lennon L. Whincup P.H. Hepatic enzymes, the metabolic syndrome, and the risk of type 2 diabetes in older men.Diabetes Care. 2005; 28: 2913-18Crossref PubMed Scopus (217) Google Scholar, 5Hanley A.J. Williams K. Festa A. Wagenknecht L.E. D’Agostino Jr, R.B. Haffner S.M. Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study.Diabetes. 2005; 54: 3140-7Crossref PubMed Scopus (346) Google Scholar] and atherothrombotic risk factors [17Cigolini M. Targher G. Agostino G. Tonoli M. Muggeo M. De Sandre G. Liver steatosis and its relation to plasma haemostatic factors in apparently healthy men – role of the metabolic syndrome.Thromb Haemost. 1996; 76: 69-73Crossref PubMed Scopus (83) Google Scholar, 18Targher G. Bertolini L. Scala L. Zoppini G. Zenari L. Falezza G. Non‐alcoholic hepatic steatosis and its relation to increased plasma biomarkers of inflammation and endothelial dysfunction in non‐diabetic men. Role of visceral adipose tissue.Diabet Med. 2005; 22: 1354-8Crossref PubMed Scopus (152) Google Scholar]. There is significant clustering of coagulation and fibrinolytic proteins along with metabolic features with insulin resistance in apparently healthy South Asians, and probably ALT is a significant part of that cluster[19Kain K. Catto A.J. Grant P.J. Associations between insulin resistance and thrombotic risk factors in high‐risk South Asian subjects.Diabet Med. 2003; 20: 651-5Crossref PubMed Scopus (35) Google Scholar]. However, there was no independent correlation for ALT with either PAI‐1 antigen or t‐PA when variables that are features of metabolic syndrome were put in the regression model, so fibrinolysis cannot be proposed as a surrogate or substitute index for routine metabolic syndrome criteria. An asymptomatic raised ALT in the absence of liver disease or heavy alcohol intake reflects liver fat deposition, and therefore represents NAFLD, especially in individuals with features of the metabolic syndrome and insulin resistance [20Clark J.M. Brancati F.L. Diehl A.M. Nonalcoholic fatty liver disease.Gastroenterology. 2002; 122: 1649-57Abstract Full Text Full Text PDF PubMed Scopus (770) Google Scholar, 21Daniel S. Ben Menachem T. Vasudevan G. Ma C.K. Blumenkehl M. Prospective evaluation of unexplained chronic liver transaminase abnormalities in asymptomatic and symptomatic patients.Am J Gastroenterol. 1999; 94: 3010-14Crossref PubMed Scopus (318) Google Scholar]. An incidence of elevated (cut‐off above the normal range) ALT of 24% is possibly an underrepresentation of asymptomatic and undiagnosed hepatic steatosis in an apparently healthy South Asian population [22Jeong S.K. Nam H.S. Rhee J.A. Shin J.H. Kim J.M. Cho K.H. Metabolic syndrome and ALT: a community study in adult Koreans.Int J Obes Relat Metab Disord. 2004; 28: 1033-8Crossref PubMed Scopus (46) Google Scholar, 23Mofrad P. Contos M.J. Haque M. Sargeant C. Fisher R.A. Luketic V.A. Sterling R.K. Shiffman M.L. Stravitz R.T. Sanyal A.J. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values.Hepatology. 2003; 37: 1286-92Crossref PubMed Scopus (890) Google Scholar], especially because they are a group with increased visceral fat, insulin resistance and metabolic syndrome incidence, despite having an apparently normal BMI. As well as being associated with T2DM and CVD, hepatic steatosis in NAFLD is associated with a small but appreciable increased risk of hepatic fibrosis, cirrhosis and hepatocellular carcinoma in Caucasian subjects [24Ratziu V. Poynard T. Assessing the outcome of nonalcoholic steatohepatitis? It’s time to get serious.Hepatology. 2006; 44: 802-5Crossref PubMed Scopus (60) Google Scholar, 25Bugianesi E. Leone N. Vanni E. Marchesini G. Brunello F. Carucci P. Musso A. De Paolis P. Capussotti L. Salizzoni M. Rizzetto M. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma.Gastroenterology. 2002; 123: 134-40Abstract Full Text Full Text PDF PubMed Scopus (1264) Google Scholar]. Although we believe that the raised ALT in this study is likely to reflect liver fat, on the basis of previous information from Caucasian studies, we do not have data from ultrasound imaging or liver biopsies to confirm this. In addition, we do not have any hepatitis serology data, or indeed any other biochemical assessment, to exclude rare forms of liver disease, and were reliant on self‐reporting of alcohol intake. Despite these limitations, it is generally accepted that the incidence of alcoholism is very low in South Asians, as is the rate of hepatitis B and C infection [26Anand S.S. Yusuf S. Risk factors for cardiovascular disease in Canadians of South Asian and European origin: a pilot study of the Study of Heart Assessment and Risk in Ethnic Groups (SHARE).Clin Invest Med. 1997; 20: 204-10PubMed Google Scholar, 27Hahne S. Ramsay M. Balogun K. Edmunds W.J. Mortimer P. Incidence and routes of transmission of hepatitis B virus in England and Wales, 1995–2000: implications for immunisation policy.J Clin Virol. 2004; 29: 211-20Crossref PubMed Scopus (135) Google Scholar, 28Gray H. Wreghitt T. Stratton I.M. Alexander G.J. Turner R.C. O’Rahilly S. High prevalence of hepatitis C infection in Afro‐Caribbean patients with type 2 diabetes and abnormal liver function tests.Diabet Med. 1995; 12: 244-9Crossref PubMed Scopus (117) Google Scholar], making it unlikely that these factors play a significant role in producing the elevated ALT in South Asian subjects. There are more than a billion people in South Asia, and the growing incidence of diabetes and obesity among them (the projected greatest absolute increase in the number of people with diabetes predicted by 2030 will be in India) continues to be a colossal worldwide public health problem [29Wild S. Roglic G. Green A. Sicree R. King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030.Diabetes Care. 2004; 27: 1047-53Crossref PubMed Scopus (11978) Google Scholar]. The presence of an elevated ALT, which is a simple, routine, readily available, inexpensive measurement, may help to readily identify individuals who are likely to have insulin resistance and the associated cluster of cardiovascular and thrombotic risk factors, and who are therefore at particularly high risk of developing T2DM and CVD. This might have implications for cardiovascular risk reduction strategies, and potential health economics. The utility of this would clearly need to be confirmed, but the need to demonstrate this is particularly important in view of the lack of ability of traditional risk factors to predict these diseases. The relationship between ALT and cardiac–metabolic–thrombotic risk factors is likely to be due to ethnic differences in visceral fat distribution. In view of the epidemiologic studies demonstrating an increased risk of T2DM and CVD with increasing ALT, it is necessary for large‐scale prospective studies to be performed in South Asian subjects to ascertain whether they have similar or even an increased risk of developing morbidity and mortality due to T2DM and CVD, dependent on their ALT. Moreover, there is a need to establish the relationship of ALT to the prevalence and natural history of NAFLD. The Stroke Association funded this study. The authors state that they have no conflict of interest." @default.
• W1539779969 created "2016-06-24" @default.
• W1539779969 creator A5036249431 @default.
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• W1539779969 date "2008-05-01" @default.
• W1539779969 modified "2023-09-30" @default.
• W1539779969 title "Alanine aminotransferase is associated with atherothrombotic risk factors in a British South Asian population" @default.
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